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JAMA Neurology Nov 2023Emerging evidence suggests that progression independent of relapse activity (PIRA) is a substantial contributor to long-term disability accumulation in...
IMPORTANCE
Emerging evidence suggests that progression independent of relapse activity (PIRA) is a substantial contributor to long-term disability accumulation in relapsing-remitting multiple sclerosis (RRMS). To date, there is no uniform agreed-upon definition of PIRA, limiting the comparability of published studies.
OBJECTIVE
To summarize the current evidence about PIRA based on a systematic review, to discuss the various terminologies used in the context of PIRA, and to propose a harmonized definition for PIRA for use in clinical practice and future trials.
EVIDENCE REVIEW
A literature search was conducted using the search terms multiple sclerosis, PIRA, progression independent of relapse activity, silent progression, and progression unrelated to relapses in PubMed, Embase, Cochrane, and Web of Science, published between January 1990 and December 2022.
FINDINGS
Of 119 identified single records, 48 eligible studies were analyzed. PIRA was reported to occur in roughly 5% of all patients with RRMS per annum, causing at least 50% of all disability accrual events in typical RRMS. The proportion of PIRA vs relapse-associated worsening increased with age, longer disease duration, and, despite lower absolute event numbers, potent suppression of relapses by highly effective disease-modifying therapy. However, different studies used various definitions of PIRA, rendering the comparability of studies difficult.
CONCLUSION AND RELEVANCE
PIRA is the most frequent manifestation of disability accumulation across the full spectrum of traditional MS phenotypes, including clinically isolated syndrome and early RRMS. The harmonized definition suggested here may improve the comparability of results in current and future cohorts and data sets.
Topics: Humans; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Chronic Disease; Recurrence; PubMed; Disease Progression
PubMed: 37782515
DOI: 10.1001/jamaneurol.2023.3331 -
Multiple Sclerosis and Related Disorders Aug 2017There is evidence for the benefits of exercise training in persons with multiple sclerosis (MS). However, these benefits have primarily been established in individuals... (Review)
Review
INTRODUCTION
There is evidence for the benefits of exercise training in persons with multiple sclerosis (MS). However, these benefits have primarily been established in individuals with mild-to-moderate disability (i.e., Expanded Disability Status Scale [EDSS] scores 1.0-5.5), rather than among those with significant mobility impairment. Further, the approaches to exercise training that have been effective in persons with mild-to-moderate MS disability may not be physically accessible for individuals with mobility limitations. Therefore, there is a demand for an evidence-base on the benefits of physically accessible exercise training approaches for managing disability in people with MS with mobility impairment.
OBJECTIVE
To conduct a systematic review of the current literature pertaining to exercise training in individuals with multiple sclerosis (MS) with severe mobility disability.
METHODS
Four electronic databases (PubMed, EMBASE, OvidMEDLINE, and PsychINFO) were searched for relevant articles published up until October 2016. The review focused on English-language studies that examined the effect of exercise training in people with MS with severe mobility disability, characterized as the need for assistance in ambulation or EDSS score ≥ 6.0. The inclusion criteria involved full-text articles that: (i) included participants with a diagnosis of MS; (ii) included primarily participants with a reported EDSS score ≥ 6.0 and/or definitively described disability consistent with this level of neurological impairment; and (iii) implemented a prospective, structured exercise intervention. Data were analyzed using a descriptive approach and summarized by exercise training modality (conventional or adapted exercise training), and by outcome (disability, physical fitness, physical function, and symptoms and participation).
RESULTS
Initially, 1164 articles were identified and after removal of duplicates, 530 articles remained. In total, 512 articles did not meet the inclusion criteria. 19 articles were included in the final review. Five studies examined conventional exercise training (aerobic and resistance training), and thirteen studies examined adapted exercise modalities including body-weight support treadmill training (BWSTT), total-body recumbent stepper training (TBRST), and electrical stimulation cycling (ESAC). Outcomes related to mobility, fatigue, and quality of life (QOL) were most frequently reported. Two of five studies examining conventional resistance exercise training reported significant improvements in physical fitness, physical function, and/or symptomatic and participatory outcomes. Nine of 13 studies examining adapted exercise training reported significant improvements in disability, physical fitness, physical function, and/or symptomatic and participatory outcomes.
CONCLUSIONS
There is limited, but promising evidence for the benefits of exercise training in persons with MS with severe mobility disability. Considering the lack of effective therapeutic strategies for managing long-term disability accumulation, exercise training could be considered as an alternative approach. Further research is necessary to optimize the prescription and efficacy of exercise training for adults with MS with severe mobility disability.
Topics: Disability Evaluation; Exercise Therapy; Humans; Movement Disorders; Multiple Sclerosis
PubMed: 28755682
DOI: 10.1016/j.msard.2017.06.003 -
The Cochrane Database of Systematic... Jan 2017Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing and remitting disease that usually causes weakness and sensory... (Review)
Review
BACKGROUND
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing and remitting disease that usually causes weakness and sensory loss. The symptoms are due to autoimmune inflammation of peripheral nerves. CIPD affects about 2 to 3 per 100,000 of the population. More than half of affected people cannot walk unaided when symptoms are at their worst. CIDP usually responds to treatments that reduce inflammation, but there is disagreement about which treatment is most effective.
OBJECTIVES
To summarise the evidence from Cochrane systematic reviews (CSRs) and non-Cochrane systematic reviews of any treatment for CIDP and to compare the effects of treatments.
METHODS
We considered all systematic reviews of randomised controlled trials (RCTs) of any treatment for any form of CIDP. We reported their primary outcomes, giving priority to change in disability after 12 months.Two overview authors independently identified published systematic reviews for inclusion and collected data. We reported the quality of evidence using GRADE criteria. Two other review authors independently checked review selection, data extraction and quality assessments.On 31 October 2016, we searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (in theCochrane Library), MEDLINE, Embase, and CINAHL Plus for systematic reviews of CIDP. We supplemented the RCTs in the existing CSRs by searching on the same date for RCTs of any treatment of CIDP (including treatment of fatigue or pain in CIDP), in the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL Plus.
MAIN RESULTS
Five CSRs met our inclusion criteria. We identified 23 randomised trials, of which 15 had been included in these CSRs. We were unable to compare treatments as originally planned, because outcomes and outcome intervals differed. CorticosteroidsIt is uncertain whether daily oral prednisone improved impairment compared to no treatment because the quality of the evidence was very low (1 trial, 28 participants). According to moderate-quality evidence (1 trial, 41 participants), six months' treatment with high-dose monthly oral dexamethasone did not improve disability more than daily oral prednisolone. Observational studies tell us that prolonged use of corticosteroids sometimes causes serious side-effects. Plasma exchangeAccording to moderate-quality evidence (2 trials, 59 participants), twice-weekly plasma exchange produced more short-term improvement in disability than sham exchange. In the largest observational study, 3.9% of plasma exchange procedures had complications. Intravenous immunoglobulinAccording to high-quality evidence (5 trials, 269 participants), intravenous immunoglobulin (IVIg) produced more short-term improvement than placebo. Adverse events were more common with IVIg than placebo (high-quality evidence), but serious adverse events were not (moderate-quality evidence, 3 trials, 315 participants). One trial with 19 participants provided moderate-quality evidence of little or no difference in short-term improvement of impairment with plasma exchange in comparison to IVIg. There was little or no difference in short-term improvement of disability with IVIg in comparison to oral prednisolone (moderate-quality evidence; 1 trial, 29 participants) or intravenous methylprednisolone (high-quality evidence; 1 trial, 45 participants). One unpublished randomised open trial with 35 participants found little or no difference in disability after three months of IVIg compared to oral prednisone; this trial has not yet been included in a CSR. We know from observational studies that serious adverse events related to IVIg do occur. Other immunomodulatory treatmentsIt is uncertain whether the addition of azathioprine (2 mg/kg) to prednisone improved impairment in comparison to prednisone alone, as the quality of the evidence is very low (1 trial, 27 participants). Observational studies show that adverse effects truncate treatment in 10% of people.According to low-quality evidence (1 trial, 60 participants), compared to placebo, methotrexate 15 mg/kg did not allow more participants to reduce corticosteroid or IVIg doses by 20%. Serious adverse events were no more common with methotrexate than with placebo, but observational studies show that methotrexate can cause teratogenicity, abnormal liver function, and pulmonary fibrosis.According to moderate-quality evidence (2 trials, 77 participants), interferon beta-1a (IFN beta-1a) in comparison to placebo, did not allow more people to withdraw from IVIg. According to moderate-quality evidence, serious adverse events were no more common with IFN beta-1a than with placebo.We know of no other completed trials of immunosuppressant or immunomodulatory agents for CIDP. Other treatmentsWe identified no trials of treatments for fatigue or pain in CIDP. Adverse effectsNot all trials routinely collected adverse event data; when they did, the quality of evidence was variable. Adverse effects in the short, medium, and long term occur with all interventions. We are not able to make reliable comparisons of adverse events between the interventions included in CSRs.
AUTHORS' CONCLUSIONS
We cannot be certain based on available evidence whether daily oral prednisone improves impairment compared to no treatment. However, corticosteroids are commonly used, based on widespread availability, low cost, very low-quality evidence from observational studies, and clinical experience. The weakness of the evidence does not necessarily mean that corticosteroids are ineffective. High-dose monthly oral dexamethasone for six months is probably no more or less effective than daily oral prednisolone. Plasma exchange produces short-term improvement in impairment as determined by neurological examination, and probably produces short-term improvement in disability. IVIg produces more short-term improvement in disability than placebo and more adverse events, although serious side effects are probably no more common than with placebo. There is no clear difference in short-term improvement in impairment with IVIg when compared with intravenous methylprednisolone and probably no improvement when compared with either oral prednisolone or plasma exchange. According to observational studies, adverse events related to difficult venous access, use of citrate, and haemodynamic changes occur in 3% to17% of plasma exchange procedures.It is uncertain whether azathioprine is of benefit as the quality of evidence is very low. Methotrexate may not be of benefit and IFN beta-1a is probably not of benefit.We need further research to identify predictors of response to different treatments and to compare their long-term benefits, safety and cost-effectiveness. There is a need for more randomised trials of immunosuppressive and immunomodulatory agents, routes of administration, and treatments for symptoms of CIDP.
Topics: Adrenal Cortex Hormones; Azathioprine; Dexamethasone; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Interferon beta-1a; Methotrexate; Methylprednisolone; Plasma Exchange; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Prednisone; Randomized Controlled Trials as Topic; Review Literature as Topic
PubMed: 28084646
DOI: 10.1002/14651858.CD010369.pub2 -
Medicina (Kaunas, Lithuania) Nov 2019People with multiple sclerosis (MS) often experience limitations in joint range of motion, which is linked to spasticity and continued inactivity. Low flexibility... (Meta-Analysis)
Meta-Analysis
People with multiple sclerosis (MS) often experience limitations in joint range of motion, which is linked to spasticity and continued inactivity. Low flexibility levels in this population have been linked to postural problems and muscular pain. Therefore, the purpose of this study was to conduct a systematic review and a meta-analysis aimed at identifying the characteristics and methodological quality of investigations studying the effects of exercise interventions on the flexibility levels of people with MS. Three electronic databases (MEDLINE/PubMed, SPORTDiscus and Scopus) were systematically searched up to May 2019 for intervention studies focused on the effects of exercise on the flexibility levels of people with MS. A meta-analysis, including randomized controlled trials (RCT), which reported information regarding the effects of exercise on flexibility, was also conducted. The methodological quality of included studies was assessed using the Physiotherapy Evidence Database, and the Quality Assessment Tool for Before-After Studies, with no control group. The quality of the information reported, regarding the programs conducted, was assessed by means of the Consensus on Exercise Reporting Template (CERT) scale. Seven studies, four RCTs and three uncontrolled investigations were finally selected. The methodological quality of the RCTs was considered "poor" in one study, and "good" and "excellent" in two studies and one investigation, respectively. The three uncontrolled studies showed a methodological quality between "fair" and "poor". Following the CERT scale, four studies were graded as "high" and three as "low". Findings from the meta-analysis indicated no significant effects on hamstring flexibility, or the range of motion in the hips, knees or ankles. There is preliminary evidence from individual studies which indicates that people with MS can improve their lower limb flexibility following participation in physical exercise programs, but the meta-analysis did not confirm these findings.
Topics: Exercise Therapy; Humans; Multiple Sclerosis; Pliability; Range of Motion, Articular
PubMed: 31684026
DOI: 10.3390/medicina55110726 -
Neurology India 2021Multiple sclerosis is a chronic demyelinating disorder with a myriad of imaging and clinical features that overlap with number of other neurological conditions.... (Review)
Review
BACKGROUND
Multiple sclerosis is a chronic demyelinating disorder with a myriad of imaging and clinical features that overlap with number of other neurological conditions. Incorrect diagnosis poses a significant risk to patients, it may lead to delays in management, increased morbidity, and also adds to the financial cost.
OBJECTIVE
The aim of this study was to highlight strategies for the efficient differentiation of multiple sclerosis from other diseases which may masquerade as MS clinico-radiologically.
MATERIAL AND METHODS
A systematic literature review was conducted through online databases including PubMed and Medline. Relevant publications on radiological aspects of multiple sclerosis, white matter diseases and mimickers of Multiple sclerosis were included in the analysis.
RESULTS
Common mimickers of MS include small vessel disease, acute disseminated encephalomyelitis, neuromyelitis optica, anti-MOG encephalomyelitis, vasculitis, and CADASIL. Contrast-enhanced MRI study performed using MS protocol on high strength MRI system evaluated following a structured protocol along with clinical correlation is effective in differentiating MS from its mimickers.
CONCLUSIONS
Contrast-enhanced MRI performed on a high strength scanner using MS protocol with structured protocol for evaluation along, with a better collaboration between radiologists and clinicians may help in minimizing errors in diagnosis of multiple sclerosis.
Topics: Encephalomyelitis; Encephalomyelitis, Acute Disseminated; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Neuromyelitis Optica
PubMed: 34979638
DOI: 10.4103/0028-3886.333497 -
Journal of Neurology Feb 2022Since the declaration of COVID-19 pandemic, several case reports of demyelination of both peripheral and central nervous systems have been published. The association... (Review)
Review
BACKGROUND
Since the declaration of COVID-19 pandemic, several case reports of demyelination of both peripheral and central nervous systems have been published. The association between CNS demyelination and viral infection has long been documented, and this link was recently reported following SARS-CoV-2 infection as well.
OBJECTIVES
In this systematic review, we aim to investigate the existing literature on CNS demyelination associated with SARS-CoV-2, and the proposed pathophysiological mechanisms.
METHODS
We conducted a systematic review of articles in PubMed, SCOPUS, EMBASE, Cochrane, Google Scholar and Ovid databases, from 1 January 2020 until June 15, 2021. The following keywords were used: "COVID-19", "SARS-CoV-2", "demyelination", "demyelinating disease", "multiple sclerosis", "neuromyelitis optica", and "transverse myelitis".
RESULTS
A total of 60 articles were included in the final analysis of this systematic review and included 102 patients: 52 (51%) men and 50 (49%) women, with a median age of 46.5 years. The demyelination mimicked a variety of conditions with a picture of encephalitis/encephalomyelitis being the most common. At the same time other patterns were less frequently reported such as MS, NMOSD and even MOGAD. Longitudinally extensive transverse myelitis (LETM) was the most frequently reported pattern of spinal cord involvement.
CONCLUSION
A growing body of literature has shown an association between SARS-CoV-2 infection and the development of different types of CNS demyelination. Although causality cannot readily be inferred, this review may suggest a probable causal relationship, through a para-infectious or post-infectious immune-mediated etiology in COVID-19 patients. This relationship needs to be clarified in future research.
Topics: COVID-19; Female; Humans; Male; Middle Aged; Myelitis, Transverse; Neuromyelitis Optica; Pandemics; SARS-CoV-2
PubMed: 34386902
DOI: 10.1007/s00415-021-10752-x -
Multiple Sclerosis and Related Disorders Jul 2023Epidemiological studies have shown conflicting results between antibiotic use and multiple sclerosis (MS) risks. The present systematic review and meta-analysis were... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epidemiological studies have shown conflicting results between antibiotic use and multiple sclerosis (MS) risks. The present systematic review and meta-analysis were conducted to assess the association between antibiotic use and the risk of MS.
METHODS
PubMed, Scopus, Embase, Web of Science, and Google Scholar as well as reference lists of retrieved studies were searched systematically to identify studies were assessed the relationship between antibiotic use and MS up to September 24, 2022. Random-effects model was used for the calculation of pooled Odds ratio (OR) and 95% confidence intervals (CI).
RESULTS
Five independent studies containing 47,491 participants were included in the meta-analysis. The overall results of included studies showed a non-significant positive association between antibiotic use (OR overall=1.01, 95%CI: 0.75-1.37) and a non-significant negative association between penicillin use (OR overall= 0.83; 95%CI: 0.62-1.13) and MS risk. Heterogeneity was (I=90.1, P < 0.001) and (I=90.7, P < 0.001) in antibiotics and penicillin use groups respectively.
CONCLUSION
Our meta-analysis did not show a significant association between antibiotic or penicillin use with the risk of MS. However, due to the limitations of this study, further well-designed studies are required to confirm our findings.
Topics: Humans; Anti-Bacterial Agents; Multiple Sclerosis; Penicillins; Odds Ratio
PubMed: 37209499
DOI: 10.1016/j.msard.2023.104765 -
The Cochrane Database of Systematic... Jun 2023Multiple sclerosis (MS) is an autoimmune, T-cell-dependent, inflammatory, demyelinating disease of the central nervous system, with an unpredictable course. Current MS... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is an autoimmune, T-cell-dependent, inflammatory, demyelinating disease of the central nervous system, with an unpredictable course. Current MS therapies focus on treating and preventing exacerbations, and avoiding the progression of disability. At present, there is no treatment that is capable of safely and effectively reaching these objectives. Clinical trials suggest that alemtuzumab, a humanized monoclonal antibody, could be a promising option for MS.
OBJECTIVES
To evaluate the benefits and harms of alemtuzumab alone or associated with other treatments in people with any form of MS.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 21 June 2022.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in adults with any subtype of MS comparing alemtuzumab alone or associated with other medications versus placebo; another active drug; or alemtuzumab in another dose, regimen, or duration.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our co-primary outcomes were 1. relapse-free survival, 2. sustained disease progression, and 3. number of participants experiencing at least one adverse event. Our secondary outcomes were 4. participants free of clinical disability, 5. quality of life, 6. change in disability, 7. fatigue, 8. new or enlarging lesions on resonance imaging, and 9. dropouts. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We included three RCTs (1713 participants) comparing intravenous alemtuzumab versus subcutaneous interferon beta-1a for relapsing-remitting MS. Participants were treatment-naive (two studies) or had experienced at least one relapse after interferon or glatiramer (one study). Alemtuzumab was given at doses of 12 mg/day or 24 mg/day for five days at months 0 and 12, or 24 mg/day for three days at months 12 and 24. Participants in the interferon beta-1a group received 44 μg three times weekly. Alemtuzumab 12 mg: 1. may improve relapse-free survival at 36 months (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.18 to 0.53; 1 study, 221 participants; low-certainty evidence); 2. may improve sustained disease progression-free survival at 36 months (HR 0.25, 95% CI 0.11 to 0.56; 1 study, 223 participants; low-certainty evidence); 3. may make little to no difference on the proportion of participants with at least one adverse event at 36 months (risk ratio [RR] 1.00, 95% CI 0.98 to 1.02; 1 study, 224 participants; low-certainty evidence), although the proportion of participants with at least one adverse event was high with both drugs; 4. may slightly reduce disability at 36 months (mean difference [MD] -0.70, 95% CI -1.04 to -0.36; 1 study, 223 participants; low-certainty evidence). The evidence is very uncertain regarding the risk of dropouts at 36 months (RR 0.81, 95% CI 0.57 to 1.14; 1 study, 224 participants; very low-certainty evidence). Alemtuzumab 24 mg: 1. may improve relapse-free survival at 36 months (HR 0.21, 95% CI 0.11 to 0.40; 1 study, 221 participants; low-certainty evidence); 2. may improve sustained disease progression-free survival at 36 months (HR 0.33, 95% CI 0.16 to 0.69; 1 study, 221 participants; low-certainty evidence); 3. may make little to no difference on the proportion of participants with at least one adverse event at 36 months (RR 0.99, 95% CI 0.97 to 1.02; 1 study, 215 participants; low-certainty evidence), although the proportion of participants with at least one adverse event was high with both drugs; 4. may slightly reduce disability at 36 months (MD -0.83, 95% CI -1.16 to -0.50; 1 study, 221 participants; low-certainty evidence); 5. may reduce the risk of dropouts at 36 months (RR 0.08, 95% CI 0.01 to 0.57; 1 study, 215 participants; low-certainty evidence). For quality of life, fatigue, and participants free of clinical disease activity, the studies either did not consider these outcomes or they used different measuring tools to those planned in this review.
AUTHORS' CONCLUSIONS
Compared with interferon beta-1a, alemtuzumab may improve relapse-free survival and sustained disease progression-free survival, and make little to no difference on the proportion of participants with at least one adverse event for people with relapsing-remitting MS at 36 months. The certainty of the evidence for these results was very low to low.
Topics: Adult; Humans; Alemtuzumab; Interferon beta-1a; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Neoplasm Recurrence, Local
PubMed: 37272540
DOI: 10.1002/14651858.CD011203.pub3 -
Multiple Sclerosis and Related Disorders Dec 2023Persons with multiple sclerosis (MS) engage in less physical activity than the general population, and the disease manifestations and comorbidity conditions might... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Persons with multiple sclerosis (MS) engage in less physical activity than the general population, and the disease manifestations and comorbidity conditions might further predispose them toward sedentary behavior (SB) among this population. We performed a systematic review with meta-analysis of studies that compared SB in persons with MS and non-MS controls, and examined factors that may moderate the difference in SB between the two groups.
METHODS
We conducted a systematic search using PubMed, PsycINFO, Scopus, and CINAHL from inception up to August 2022, and identified studies that involved group comparison of SB outcomes between MS and non-MS controls. Effect sizes were calculated as standardized mean differences (SMDs) using Hedge's g. We generated a multilevel random-effects model for estimating an overall effect, and performed moderator analyses. Methodological quality was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS tool).
RESULTS
Eleven studies were included (1403 MS vs. 449 controls) and yielded 17 effects for meta-analysis. Results indicated an overall small, but significant effect (SMD [95% CI] = 0.27 [0.02, 0.53], p = 0.03) with significant heterogeneity (Q = 72.2, p < 0.01; I = 75.8%). There were larger effects when the MS sample had a higher proportion of females, or when SB was reported as percent sedentary time per day compared with other SB outcomes (p = 0.03 and 0.05, respectively). The included studies achieved fairly good quality (91.4%) using the AXIS tool.
CONCLUSIONS
The cumulative evidence supports that persons with MS engage in more SB than non-MS controls. Our findings may support the design of targeted behavioral change interventions for reducing SB and improving health and function in the MS population.
Topics: Female; Humans; Sedentary Behavior; Multiple Sclerosis; Cross-Sectional Studies; Exercise
PubMed: 37956522
DOI: 10.1016/j.msard.2023.105124 -
European Journal of Neurology Oct 2023Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While... (Review)
Review
BACKGROUND
Differentiating neuromyelitis optica spectrum disorder (NMOSD) from its mimics is crucial to avoid misdiagnosis, especially in the absence of aquaporin-4-IgG. While multiple sclerosis (MS) and myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD) represent major and well-defined differential diagnoses, non-demyelinating NMOSD mimics remain poorly characterized.
METHODS
We conducted a systematic review on PubMed/MEDLINE to identify reports of patients with non-demyelinating disorders that mimicked or were misdiagnosed as NMOSD. Three novel cases seen at the authors' institutions were also included. The characteristics of NMOSD mimics were analyzed and red flags associated with misdiagnosis identified.
RESULTS
A total of 68 patients were included; 35 (52%) were female. Median age at symptoms onset was 44 (range, 1-78) years. Fifty-six (82%) patients did not fulfil the 2015 NMOSD diagnostic criteria. The clinical syndromes misinterpreted for NMOSD were myelopathy (41%), myelopathy + optic neuropathy (41%), optic neuropathy (6%), or other (12%). Alternative etiologies included genetic/metabolic disorders, neoplasms, infections, vascular disorders, spondylosis, and other immune-mediated disorders. Common red flags associated with misdiagnosis were lack of cerebrospinal fluid (CSF) pleocytosis (57%), lack of response to immunotherapy (55%), progressive disease course (54%), and lack of magnetic resonance imaging gadolinium enhancement (31%). Aquaporin-4-IgG positivity was detected in five patients by enzyme-linked immunosorbent assay (n = 2), cell-based assay (n = 2: serum, 1; CSF, 1), and non-specified assay (n = 1).
CONCLUSIONS
The spectrum of NMOSD mimics is broad. Misdiagnosis frequently results from incorrect application of diagnostic criteria, in patients with multiple identifiable red flags. False aquaporin-4-IgG positivity, generally from nonspecific testing assays, may rarely contribute to misdiagnosis.
Topics: Humans; Female; Male; Neuromyelitis Optica; Contrast Media; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Gadolinium; Aquaporin 4; Spinal Cord Diseases; Immunoglobulin G
PubMed: 37433584
DOI: 10.1111/ene.15983